The objective of the proposed research is to develop an in vivo method for monitoring drug delivery and action in real time, in combination with precise targeting of drugs to specific cell types and intracellular targets. A magnetic probe will be developed that specifically localizes to lymphoma cells via a two-tiered targeting method. First, a ligand will be covalently attached to the probes. This ligand will direct localization to lymphoma cells via receptor-mediated endocytosis. A second ligand composed of a peptide will covalently link individual probes. This peptide contains a site that can be cleaved by an intracellular protease that is overexpressed in lymphoma cells. When the peptide is cleaved, the probes dissociate and their magnetic properties change. Magnetic resonance imaging in a living animal can easily detect this change. Once the lymphoma cells are faithfully targeted and detected via this method, a similar mechanism will be employed to target a specific drug. For example, protease inhibitors will be administered to the targeted cell. Real-time feedback of drug activity is achieved by co-administering the protease-reporter probes. The ultimate goal is to efficiently translate the technique from mice to humans for noninvasive characterization of drug action. [unreadable] [unreadable]